Perioculomotor area and alcohol

眼动周区（毛）是大脑中神经肽尿皮质素1 （Ucn1）的主要来源。Ucn1是一种与促肾上腺皮质激素释放因子（CRF）相关的内源性肽，对CRF受体的亲和力高于CRF本身。除了毛中含有ucn1的细胞（plllu）外，毛中还含有多巴胺能神经元（pillda）。本研究前几年进行的实验有力地证实了毛神经元参与酒精消耗的调节。在四方面的研究中积累了这种参与的明确证据：1)小鼠和大鼠的枕状神经元在自我给药后优先被激活；2)在选择性繁育的小鼠和大鼠中，脐部Ucn1免疫反应性与酒精摄入量呈正相关；3) C57BLl6J小鼠毛电损伤选择性阻断酒精偏好；4)将Ucn1微量注射到plllu靶区之一的侧隔膜，选择性地减少酒精摄入量。综上所述，这些研究有力地暗示了毛神经元对酒精消耗的调节。本应用程序建议扩展这些研究，以了解这种调节的机制。我们假设pllla通过各自的中心预测促进酒精消费，而plllu则减少酒精消费。本研究的主要目的是通过表征毛毛和拔毛的投影来解决我们的假设，并通过测试毛毛在酒精摄入中的作用。为了实现这一目标，我们提出了三个具体目标：1)利用神经解剖学示迹方法表征近交系C57BLl6J （C57）小鼠的毛突和毛突区域的投影分布；2)利用Ucn1敲除小鼠，检验毛损伤对酒精摄入的影响是否独立于Ucn1的功能；3)通过对C57小鼠毛内注射多巴胺激动剂，检测毛在酒精消耗中的重要性。这些研究将提供新的重要信息，说明这些最近发现的神经元是如何强有力地调节酒精摄入的。

Theperioculomotor area (pili) is the main source of neuropeptide Urocortin 1 (Ucn1 lin the brain. Ucn1 is an endogenous peptide related to the corticotropin-releasing factor (CRF) that has higher affinity to CRF receptors than CRF itself. In addition to the Ucn1-containing cells of pili (plllu), theplll area also contains a population of dopaminergic neurons (pillda). Experiments perfornied in the previous years of this R01 have strongly confirmed the involvement of pili neurons in the regulation of alcohol consumption. Definitive evidence for this involvement accumulated across four lines of research: 1) the piliu neurons are preferentially activated following alcohol self-administration in mice and rats; 2) Ucn1 immunoreactivity in piliu is positively correlated with alcohol intake in selectively-bred mouse and rat lines; 3) electrolytic lesions of pili selectively block alcohol preference in C57BLl6J mice; 4) microinjection of Ucn1 into the lateral septum, one of the target areas of plllu, selectively attenuates alcohol intake. Taken together these studies robustly implicate the pili neurons in the regulation of alcohol consumption. This application proposes to extend these studies to understand the mechanisms of this regulation. We hypothesize that pllldapromotes alcohol consumption, while plllu decreases alcohol consumption through their respective central projections. The main goal of this study is to address our hypothesis by characterizing the projectioTIs from pilida and plllu, and by testing the role of pilida in alcohol intake. To achieve thisgoal we prOpose three specific aims: 1) To characterize the distribution of prOjections from the piliu and pilida area of inbred C57BLl6J (C57) mice using neuroanatdrnical tracing approaches; 2) To test whether the effects of pili lesions on alcohol intake are independent of the functions of Ucn1 using Ucn1 knockout mice; 3) To test the importance of pilida in alcohol consumption using intracranial injections of dopamine agonists into pili of C57 mice. These studies will provide novel important information indicating how these recently identified neurons robustly regulate alcohol intake.